System and method for preparing and delivering gel

Abstract

To provide a system for forming gel for a target surface of a subject, and a method for forming gel by using the system.SOLUTION: In one embodiment, a system may have: a first container having first low-viscosity aqueous solution containing binding agent / cross-linking agent; and a second container having second low-viscosity aqueous solution containing a gelatinized component. The separate first low-viscosity aqueous solution and second low-viscosity aqueous solution are mixed, and sprayed onto a surface on which gel is formed.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. Provisional Application No. 62 / 696,261, filed July 10, 2018. The benefit of Hutchins et al. is claimed and is incorporated herein by reference in its entirety. This application was filed on 20 March 2013 by inventors James Hutchins et al. Co-pending PCT application number PCT / US19 / 4117, filed July 10, 2019 No. 8, which is hereby incorporated by reference in its entirety. Be absorbed.

[0002] 1. Field The present disclosure provides systems and methods for forming a gel on a surface. The system includes a first container having a first low-viscosity aqueous solution containing a binder / crosslinker; and and a second container having a second low-viscosity aqueous solution containing a gelling component. The first low-viscosity aqueous solution and the second low-viscosity aqueous solution are sprayed onto a surface where the solutions mix and form a gel. In addition to the system, a method is also provided. At least one of the low viscosity aqueous solutions is a deliverable product of interest, such as a vaccine. oduct of interest). [Background technology]

[0003] 2.Background 2.1 Introduction The "Background" discussion provided herein is intended to generally present the background of the disclosure. The work of the currently named inventors is within the scope of the principles described in this Background section. In some respects, and in others, aspects of the description that may not qualify as prior art at the time of filing may be None are admitted explicitly or implicitly as prior art to the present disclosure.

[0004] Gels offer the advantage that formulations adhere to surfaces and stay where they are applied The gel allows the desired product to be localized to a specific area. Therefore, many medicinal and prophylactic drugs and therapeutic treatments are formulated in the form of gels. For example, local delivery of anesthetics such as lidocaine Gels for use localize the active ingredient to the desired area of ​​interest and away from other areas. The oil also has the advantage of hydrating products that may deteriorate if dried. Drug preparations and vaccines become inactivated or ineffective when dried out.

[0005] It can be difficult to mix the active ingredient homogeneously into the gel. Application at the gel base was performed using automated mixing equipment to ensure uniform distribution of the active ingredient in the gel. The gel is prepared in a manufacturing facility at the final concentration using the same procedure. Heating the gel reduces the viscosity and facilitates mixing, but many products require higher temperatures. Does not fit.

[0006] Additionally, delivery of gels requires high pressure, which complicates some methods of delivery, such as spraying. The high viscosity of the gel or gel formulation containing the active ingredient may complicate the process. Improved methods of delivering either are needed.

[0007] In animal production facilities such as hatcheries, high throughput requirements mean hundreds of thousands, or even millions, of animals being produced daily. These treatments may include vaccinations. In poultry production facilities, these vaccines are available as concentrates that require dilution before use. Vaccines are typically prepared in batches of 5-10 L. Many batches are needed per day. For some vaccines, dilution into a gel for administration is preferred. It is difficult to mix a small vial uniformly into a larger volume of viscous gel. It is easier to mix vials with low viscosity aqueous solutions. High viscosity solutions require high pressure. It is also difficult to distribute it evenly because it requires a large amount of

[0008] 2.2. Vaccines, Apicomplexa, Eimeria, and Coccidiosis Vaccines protect humans and animals against pathogenic microorganisms, including viruses, bacteria, and parasites. In simple terms, a vaccine stimulates the immune system to recognize a specific pathogen. thereby creating a defense system that protects against future encounters with that microorganism in nature. Vaccines come in several main classes, notably inactivated or killed vaccines, subunit They can be divided into live, wild-type, and attenuated or modified live vaccines. Live and attenuated vaccines cause mild infection in recipient animals. Often, they increase the immune response to prevent a larger, possibly deadly, infection in the future. cause.

[0009] The Apicomplexa are a phylum of single-celled, spore-forming parasites with a complex life cycle. A well-known human disease caused by the phylum Picomplexa is babesiosis (Ba besia, Cryptosporidium parvum m), malaria (Plasmodium), and toxoplasmosis (Toxoplasmosis Apicomplexan diseases also affect animals and livestock. Cryptosporidium parvum and Toxoplasma gondii Some, such as T. ndii, affect both humans and animals. Other apicomplexans, such as Heileria, only affect animals. The life cycle of complex phyla is characterized by the fact that they have both sexual and asexual reproductive phases. The life cycle is often complex, with a phase in which the organism is excreted in the environment and a phase in which the organism is transported within the animal host. In many Apicomplexa, the host has several stages in its life cycle. species and other phases occur in different host species.

[0010] In contrast, Eimeria, a parasite of the Apicomplexan phylum, generally They are monospecific and monohost, meaning that their life cycle is specific to a single host species. Sporocysts are the life stage of Eimeria contained in oocysts. The porocyst) can be released prior to delivery to improve the infectivity of the vaccine. Eimeria is a company that provides a wide range of products to cattle, chickens, fish, goats, pigs, rabbits, reptiles, sheep, and other animals. It causes coccidiosis in wild and domestic vertebrates, such as turkeys. Various Eimeria species have preferred portions of the gastrointestinal (GI) tract where they reproduce and cause GI Causes damage to the ductal epithelium.

[0011] Coccidiosis is a common disease in poultry. It is usually controlled by: This is achieved using ionophores or chemicals in the feed. Environmental impacts of ionophores, ionophores and other chemicals, consumer demand, and coccidiophores. Due to the risk of the emergence of resistant bacteria, such as those from the subdivision M. polio, alternative means of control are now being sought. Vaccines against coccidiosis are used to control coccidiosis by administering ionofibrillar to the feed. However, it has the potential to dramatically reduce or eliminate the need for vaccines or chemicals. The vaccine is not widely used, in part due to a lack of uniformity with mass vaccine coverage. As currently delivered, Eimeria vaccines in poultry are an inefficient, It causes first round infectivity and immunity, This usually results in a large naive population that is susceptible to disease. The naive population then develops immunity. It relies on recycling in the breeding farm to induce infection. Their output will lead to large-scale infection of the remaining naive population. This results in a high oocyst output in the period following primary infection, which is This can lead to susceptibility to secondary bacterial infections such as erythritis, which require antibiotics to resolve. Effective vaccination of all birds today has reduced the morbidity and mortality associated with Eimeria infection. and lack of weight gain may be avoided. See No. 83663A1, Karimpour. Currently, poor performance, morbidity, and mortality The global impact of coccidiosis due to coccidiosis is estimated at $300 million. An estimated $90 million is spent annually in the United States and $3 billion worldwide to control the disease. (5m Editor, 2013, High Cost of Coccidio sis in Broilers,The Poultry Site,https: / / thepou ltrysite.com / news / 2013 / 02 / high-cost-of-coccidiosis-in-broilers). Summary of the Invention

[0012] 3. Disclosure Overview In contrast to mixing the active ingredient into a preformed gel, a two-component gel system is proposed. The system consists of two low-viscosity aqueous solutions that form a gel when mixed. The advantages of this system are ease of mixing, low pressure delivery, and prevention of dehydration upon administration.

[0013] One embodiment relates to a system for delivering a product of interest. The system comprises a first a first vessel containing a product of interest in a solution; a second vessel containing a second solution; a delivery device in fluid communication with the second container, and a delivery device outlet. The first solution comprises: The first container is moved to a first delivery device outlet to generate a first spray. The solution is transferred from the second container to a second delivery device outlet to generate a second spray. Upon delivery, the first and second solutions mix and form a gel containing the desired product. The second embodiment relates to a system for delivering a vaccine solution containing oocysts to an animal. The system comprises a first container containing unbroken oocysts in a first solution, a second container containing unbroken oocysts in a second solution, and a second container containing a liquid, a delivery device in fluid communication with the first container and the second container, and a delivery The first solution is transferred from the first container to the first delivery device outlet. The second solution is delivered from the second container to the second delivery device outlet to generate a first spray. Upon delivery, the first solution and the second solution react to produce a second mist. A gel is formed containing the oocyst solution.

[0014] Yet another embodiment involves disrupting the outer membrane of the oocysts and leaving at least some intact oocysts. The present invention relates to a system for releasing rocysts and thereafter delivering the resulting mixture to an animal. Co-pending PCT Application No. PCT / US19 / 4, filed July 10, 2019 See James Hutchins et al., No. 1178. The system comprises a first a first container containing unbroken oocysts in a liquid, a processing chamber, and a first delivery outlet The system includes a first delivery device having a second container containing a second solution, and The first solution is delivered from the first container to the treatment chamber. The oocysts are then transferred to a chamber where at least some of the oocyst membrane is destroyed and the oocysts are released. A first solution is produced which is a mixture of the sporocysts and the first delivery. The first solution is then directed to an outlet to generate a first spray, and the second solution is then directed from a second container to a second delivery device. The first solution and the second solution are then moved to the outlet of the vice to generate a second spray. The bacteria mixes with the bacteria to form a gel containing the oocysts and sporocysts.

[0015] The formulations used for delivery of oocyst-based vaccines are aqueous solutions or gels. Simple aqueous solutions usually contain oocysts which dry after spray application. Gel formulations do not provide any component to protect oocysts from drying. However, it is difficult to mix the vaccine uniformly into the high viscosity gel. It may be difficult to dispense the material into the recipient. Treatment of oocysts for sporulation can improve vaccine efficacy, but The viruses are no longer encapsulated within their natural protective carrier, the oocyst wall. Therefore, it is important to provide a protective environment to ensure viability. To form a protective gel for the test piece, the two-component system was mixed with both It can be used for spray delivery where the ingredients are low viscosity aqueous solutions. When mixed, the ingredients dissolve in the spray. It forms a protective gel that surrounds the porocysts. This solution is obtained by mixing the vaccine in a viscous solution. and / or dispensing / spraying a vaccine premixed in a high viscosity solution (e.g. gel). Avoid the difficulties associated with

[0016] A preferred commercial bird to be vaccinated by the method of the present invention is a chicken.

[0017] Preferred compositions for administration to chickens include E. tenella, E. acervuli na, E.maxima, E.necatrix, E.mitis, E.praecox , E. hagani, E. mivati, and E. brunetti. The method comprises the steps of: (a) preparing a culture of sporocysts or sporocysts and oocysts of one or more species of Eimeria; Includes mixtures.

[0018] Another preferred commercial bird to be vaccinated by the method of the present invention is the Japanese quail. It is.

[0019] A preferred composition for administration to turkeys is E. meleagrimitis, E. .adenoeides, E.gallopavonis, E.dispersa, E. meleagridis, E. innocua, and E. subrotunda Sporocysts or sporocysts and aucubins of one or more species of Eimeria selected from the group Contains a mixture of cysts.

[0020] 4. Brief description of the drawings Having thus described in general terms the various embodiments of the present disclosure, reference will now be made to the accompanying drawings, in which: The drawings are not drawn to scale and may not include all components of the system. stomach. [Brief description of the drawings]

[0021] [Figure 1] FIG. 1 is a schematic diagram of an embodiment (1) of the gel.

[0022] [Figure 2A] FIG. 2A is a graphical representation of Eimeria oocyst life stages and vaccines.

[0023] [Figure 2B] FIG. 2B is a graphical representation of the life stages of Eimeria oocysts in chickens.

[0024] [Diagram 3] FIG. 3 is a schematic diagram of gel embodiment (2).

[0025] [Figure 4] FIG. 4 is a schematic diagram of an embodiment (3) of the gel. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] 5. Detailed Description of Disclosure Various aspects of the present disclosure are described more fully below with reference to the accompanying drawings, some of which are not all. In the present disclosure, several aspects of the disclosure are presented. Indeed, the disclosure may be embodied in many different forms. The present invention should not be construed as being limited to the aspects set forth herein, but rather as being illustrative and not restrictive. This disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. It is provided as follows.

[0027] Like numbers refer to like elements throughout. In the figures, certain lines, layers, In some cases, the thickness of a component, element, or feature may be exaggerated. All publications, patent applications, patents, and other references cited herein are hereby incorporated by reference in their entireties. INCORPORATED INTO THE SPECIFICATION.

[0028] 5.1.Definition The terminology used herein is for the purpose of describing particular embodiments only. and are not intended to limit the invention.

[0029] As used herein, the term Eimeria includes E. maxima, E. miti s, E.tenella, E.acervulina, E.brunetti, E.ne catrix, E. praecox, E. hagani, E. mivati, and those means and includes Eimeria species infecting chickens consisting of any combination of . Eimeria includes E.meleagrimitis, E.adenoeides, E. .gallopavonis, E.dispersa, E.innocua, E.mel eagridis, and species that infect turkeys such as E. subrotunda , and any combination thereof. Eimeria includes E. zuernii, E. bovis, E. ellipsoidalis, and any combination thereof. Eimeria includes E. ahsata, E. bakuensis, and other species that infect E. , E. crandallis, E. faurei, E. granulosa, E. int ricata, E. marsica, E. ovinoidalis, E. pallida , E. parva, E. weybridgensis, and any combination thereof. In addition, the term Eimeria includes E. intestinalis, E. vejdo vskyi, E.piriformis, E.coecicola, E.irresid ua, E.flavescens, E.exigua, E.magna, E.perfo rans, E. media, E. stiedae, and any combination thereof .

[0030] The terms "animal" and "animal subject" include, but are not limited to, mammals and / or birds. Suitable mammalian subjects include, but are not limited to, primate subjects (e.g., Human subjects and non-human primate subjects such as monkeys, pigs, cattle (e.g., cattle), goats, horses Examples of suitable human subjects include cat, sheep, canine, murine (eg, mice, rats), and lagomorph subjects.

[0031] As used herein, the terms "avian" and "avian subject" (i.e., "bird" and " "Bird subjects" is intended to include males and females of any bird species, primarily for the production of eggs, meat, or pets. The term "poultry" is intended to include poultry that are commercially raised as livestock. "Aviary" and "avian subjects" specifically include, but are not limited to, chickens, turkeys, Ducks, geese, quails, pheasants, parakeets, parrots, cockatoos, cockatiels, ostriches, In certain embodiments, the avian subject is intended to include chickens, emus, etc. A chicken or a turkey.

[0032] As used herein, the term "low viscosity" refers to a viscosity of approximately 1 centipoise at 20 degrees Celsius. is defined.

[0033] As used herein, the term "preening" or " "Preen" is the act of chickens or other animals preening themselves or others. Ingestion of oocysts or other material through the act of grooming an animal, followed by It is defined as consuming preened material and initiating an infection.

[0034] As used herein, the term "take" in the context of vaccine infectivity, "Percent take" or "% take" , including but not limited to Eimeria after vaccination The pulmonary circulation is defined as a subject who tested positive for pulmonary circulation staining.

[0035] As used herein, the singular forms "a," "an," and "the" are used interchangeably. "The" can also be used in the plural unless the context clearly indicates otherwise. As used in this specification, the term "comprising" is intended to include "Comprising" and / or "including" refer to the stated features, steps, and / or It identifies the presence of a function, operation, element, and / or component, but does not include one or more other features, steps, It is further provided that the presence or addition of operations, elements, components, and / or groups thereof is not precluded. It is understood that the present disclosure relates to methods and methods for preparing methods comprising the steps, elements, and / or reagents set forth in the claims. , "comprise" or "consist of" as appropriate. or "consist essentially of" This can be done.

[0036] It is further noted that the claims may be drafted to exclude any optional element. Therefore, this statement may be used "solely" in conjunction with the recitation of a claim element. to use exclusive terms such as "only" or to use "negative" limitations It is intended to serve as a preliminary basis for

[0037] As used herein, the term "and / or" refers to one or more of the associated listed items. Any and all combinations of the above are included. As used herein, "between X and Y" And phrases such as "between about X and Y" should be construed to include X and Y. When used in this document, a phrase such as "between about X and Y" means "between about X and about Y." As used in the specification, a phrase such as "from about X to Y" means "from about X to about Y." Taste.

[0038] Unless otherwise defined, all terms used herein (including technical and scientific terms) are intended to be understood as meaning The terms used herein are as commonly understood by those skilled in the art to which this invention pertains. In addition, terms as defined in commonly used dictionaries have the same meaning. are to be construed to have a meaning consistent with their meaning in the context of this specification and the related art. Unless expressly defined herein, the It is understood that the description should not be construed in a formulaic sense. The order of operations (or steps) may not be described in detail for the sake of brevity and / or clarity. The order is not limited to the order shown in the claims or drawings unless otherwise indicated. I can't.

[0039] Throughout this specification, the terms "about" and / or "approximately" are used. The term "about" may be used in conjunction with numerical values ​​and / or ranges. For example, "about 40 [units]" is understood to mean a value close to 40 ±25%. Within (for example, 30 to 50), within ±20%, within ±15%, within ±10%, within ±9% Within ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, ±1%, Less than ±1% , or any other value or range of values ​​therein or below. Alternatively, depending on the context, the term "about" may mean ± one half standard deviation, ± one standard deviation, or ± two standard deviations. Additionally, the phrases "less than about [value]" or "greater than about [value]" may refer to the standard deviation of The terms "about" and "approximately" should be understood in light of the definition of the term "about" provided in "Approximately" can be used interchangeably.

[0040] Throughout this specification, numerical ranges are provided for specific amounts. These ranges are provided for those It should be understood to include all subranges within the above. So the range "50 to 80" includes all possible ranges therein (e.g., 51 ~79, 52~78, 53~77, 54~76, 55~75, 60~70, etc.). All values ​​within a stated range may be endpoints of the range encompassed thereby (e.g. For example, the range 50-80 includes ranges with endpoints such as 55-80, 50-75, etc.).

[0041] Unless otherwise defined, all technical and scientific terms used herein are , have the same meaning as commonly understood by a person skilled in the art to which this disclosure pertains. Preferred methods, devices, and materials are described herein. Any methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure. All references cited herein are hereby incorporated by reference in their entirety. To be incorporated.

[0042] 5.2.2-Component Gel Embodiments The present embodiment described below is a two-part gel system. In one embodiment, neither component is initially a gel, but when mixed, A two-component system that forms a gel is used. In a first gel embodiment, the system is A first component includes a gelling component in a low viscosity aqueous solution such as a sodium alginate solution, and a salt and a second component which is a low viscosity aqueous solution containing a binder / crosslinker such as calcium chloride solution. Each spray component is an aqueous solution with a relatively low viscosity compared to a gel, and therefore easy to mix and Facilitates spraying: low viscosity aqueous solutions can be sprayed or applied onto the target surface and mixed When the material is heated, a gel is formed. The newly formed gel can protect the material from the environment. This results in increased residence time of the gel on the surface onto which it is sprayed.

[0043] Two-component gel systems are Including but not limited to food, agriculture, military, aerospace, chemical, biochemical, pharmaceutical, nutritional supplements , cosmetics, printing and manufacturing, and any other industry where gel coating or gel application can be used. It will be appreciated that the present invention may have many applications, including those of the related art.

[0044] Examples of uses for two-part gel systems are herbicide and pesticide applications, paints, and other coating applications. Another anticipated use may include medicinal dermatological formulations applied in a two-step process. The first solution contains a first active ingredient and the second solution contains a second active ingredient. is applied to the skin, followed by the second solution. When mixed, the first and second solutions The solution forms a gel, but when the first active ingredient and the second active ingredient are mixed together, the gel is completely absorbed into the skin. They also form skin preparations.

[0045] 5.3. First Gel Embodiment The first gel embodiment 100 shown in FIG. 1 is a solution that may be a calcium chloride solution. In 102, a first reservoir 12 for holding a binder / crosslinker; , and outlet 18. The first gel embodiment 100 also includes a pump (not shown). The first gel embodiment 100 includes a first nozzle 50 in the form of a sprayer. A delivery device 46 is also included.

[0046] The first gel embodiment 100 further includes a second reservoir 86 containing a gelling component solution 90. In one embodiment, this may be a sodium alginate solution. The gel embodiment 100 includes a second delivery device in the form of a sprayer having a second nozzle 51. The second reservoir 86 includes a second reservoir outlet 88. The device is connected to a delivery device 47.

[0047] In use, the binder / crosslinker in solution 102 is pumped from the first reservoir 12 through the first nozzle 5. 0. The gelling component solution 90 is pumped from the second reservoir 86 through the second nozzle. Both the solution 102 and the solution 90 are pumped through the first and second nozzles 50. , 51 to the surface 61. In this manner, the binder / crosslinker solution 102 is delivered At some point, the spray mixes with the gelling component solution 90 on the solid surface 61 to form a gel. They may be delivered sequentially or simultaneously.

[0048] Those skilled in the art will appreciate that in another embodiment, the first reservoir 12 may contain a gelling component solution. It will be appreciated that the second reservoir 86 may contain a binder / crosslinker solution. In this alternative embodiment, when both solutions are sprayed onto the surface 61, they are gelled in their normal positions. Form a loop.

[0049] As can be appreciated, this first embodiment 100 may be used in any application where a water-based coating is used. As mentioned above, this applies to food, agriculture, manufacturing, chemical, biochemical, military, Applications include in the food, aerospace, nutritional supplement, cosmetics, printing, and pharmaceutical industries. A two-part solution as described in the subsection is one in which one or more components in the solution are reactive to another component in the solution. It is anticipated that applying the gel in a two-part solution may have the advantage that This avoids any reactivity until the solution is mixed into a gel.

[0050] 5.4. Second Gel Embodiment The life cycle of Eimeria oocysts, whether wild-type or attenuated Parts of the Eimeria oocyst in chickens are shown in Figures 2A and 2B. This figure shows an overview of the external processes that occur during the uptake of sporulation in newly hatched chickens. Chickens are vaccinated with a vaccine containing oocysts (A). The sporulated oocysts are then transferred to the chicken This process is shown in more detail in Figure 2B. This continues through an active phase, eventually resulting in the formation of unsporulated oocysts that are excreted in the chicken's faeces. Following excretion from the bird, the unsporulated oocysts survive in the environment with the aid of heat, moisture, and acid. When exposed to oxygen, it takes several days for the oocysts to sporulate (C). These sporulated oocysts are then ingested by chickens. The life cycle is then repeated.

[0051] Figure 2B shows the internal processes that occur during uptake of Eimeria oocysts in chickens. The boxed area shows a simplified diagram of the oocyst reproductive life cycle, with four The sporulated oocyst membrane containing the sporocysts is disrupted, releasing the sporocysts (D). Within each sporocyst there are two sporozoites. Enzymatic reactions in the bird's intestine digest the end caps of the sporocyst wall (not shown). The motile sporozoites then enter the intestinal tract in different regions of the intestine. They seek out and infect cells in a species-specific manner (E). For example, in chickens, E. acerv ulina infects the upper intestine, E. maxima infects the small intestine, and E. tenella , infecting the appendix.

[0052] Following infection of intestinal cells by sporozoites, the parasite's life cycle involves several stages of asexual reproduction. These life cycles continue through several stages of reproduction and amplification. unds of reproduction and amplification) This results in a significant increase in the presence of Eimeria in selected areas of the intestinal tract. After the amplification caused by the asexual phase, sexual reproduction occurs, leading to the production of oocysts. The oocysts were then shed in the feces of the chicken and were then transferred to another chicken, as shown in Figure 2A. is consumed.

[0053] The complete process takes approximately 7 days, with the exact length of time varying depending on the Eimeria species. The excystation process and subsequent invasion into the host cell occurs between days 0 and 3. The sexual reproduction stage occurs between days 3 and 5. The sexual reproduction stage and subsequent shedding of oocysts into the faeces. occurs between the 5th and 7th.

[0054] In commercial poultry operations, many birds are either not vaccinated or only partially vaccinated. Mass vaccination must optimize the frequency of vaccination in order to ensure that all vaccine recipients are vaccinated. Mass application is likely to be limited by the need for high throughput and the lack of alternative vaccination methods. A new method for high throughput is the use of Directly delivered personalized vaccination could dramatically improve vaccination. See PCT Publication No. WO 2017 / 083663Al, Karimpour. Oocysts Alternatively, the sporocysts may be sprayed directly into any opening leading to the digestive tract, such as the eyes, mouth, or nasal passages. If so, they are likely to be ingested and processed to produce the infective sporozoite life stage. The oocysts or sporocysts dispersed in the water environment will become live oocysts if not maintained in the water environment. The sporocysts and sporocysts rapidly dehydrate and die, so there may be a limited period of viability. If the oocysts and / or sporocysts are encapsulated in a gel to limit dehydration, However, as with mixing the vaccine evenly in the gel, Additionally, spraying the gel is problematic due to its high viscosity.

[0055] A second gel embodiment 110 shown in FIG. 3 is made of oleaginous cellulose suspended in a calcium chloride solution. The first reservoir 12 holds an oocyst vaccine solution 82 containing oocysts. The second gel embodiment 110 also includes a pump (not shown). The embodiment 110 also includes a first delivery device 46 in the form of a sprayer having a first nozzle 50. The first reservoir 12 is connected to the first delivery device 4 by a first reservoir outlet 18. It is connected to 6.

[0056] The second gel embodiment 110 includes a second reservoir containing a sodium alginate solution 90. 86 and a second delivery device 47 in the form of a sprayer having a second nozzle 51. The second reservoir 86 is connected to a second delivery device by a second reservoir outlet 88. It is connected to device 47.

[0057] In use, the oocyst-containing calcium chloride solution 82 is pumped from the first reservoir 12 to the first The sodium alginate solution 90 is pumped into the nozzle 50. 6 to the second nozzle 51. Both solutions 82, 90 are pumped through the first and second nozzles 51. From the nozzles 50, 51, the facial mucosa or hair of one-day-old hatchlings are directly injected. The oocysts are then simultaneously delivered to other areas of the body for grooming. The calcium solution 82 mixes with the sodium alginate solution 90 upon delivery to form a gel 62. The gel 62 is adapted to be applied when the solutions 82, 90 are delivered to the surface of the animal or during grooming. The oocysts suspended in gel62 are then ingested by the young birds. This is to avoid further risk of young birds ingesting the gel and, consequently, the oocysts while grooming. Provide opportunities for

[0058] Either calcium chloride solution or sodium alginate solution was added to the oocyst-based vaccine. It is understood that solutions 82, 90 can be mixed with cutin to achieve the same result. i.e., to form a gel-based mixture, Additionally, the first reservoir 12 contains a sodium alginate solution. and the second reservoir 86 may contain a calcium chloride solution. The oocysts are then gelled. It may be present in either of the two components for the forming system.

[0059] A preferred formulation maintains encapsulation of the oocysts or sporocysts during grooming. To ensure rapid formation of a gel with sufficient viscosity for and 3-4%, most preferably 3.5-3.8%, calcium chloride.

[0060] Propylene glycol alginate (PGA) is used instead of sodium alginate Another combination of sodium alginate and calcium chloride is calcium lactate solution or is a calcium gluconate solution and low methoxyl (LM) pectin or amidated low methoxyl (LM) pectin. Pectic acid calcium in combination with a suitable pectin-containing solution such as LMA pectin This involves the formation of a calcium gel.

[0061] 5.5. Third Gel Embodiment The third gel embodiment 120 shown in FIG. 4 is a combination of the first gel embodiment 100 and the second gel embodiment 110. The third gel embodiment includes the two-component solution described above for gel embodiment 110. The configuration 120 includes a processing system 24 for disrupting at least some of the oocyst membranes. Use of the method described above will incorporate the use of the method described above, thus placing at least some of the sporocysts in one of the two solutions. The third solution is then delivered as a spray, which when mixed together forms a gel. Gel embodiment 120 is an oocyst gel comprising oocysts suspended in calcium chloride. The third gel embodiment 120 includes a first reservoir 12 that holds a cutin solution 82. The system also includes a pump 20. A pump outlet 22 is fixed between the pump 20 and a treatment system 24. It is being done.

[0062] The third gel embodiment 120 includes a processing system 24 that includes a homogenizer 32 . The first nozzle 50 is connected to the processing system 24 .

[0063] The third gel embodiment 120 includes a third reservoir containing a sodium alginate solution 90. The third gel embodiment 120 further includes a sprayer having a second nozzle 51. The second nozzle 51 is connected to a third reservoir 86. Both the first and second delivery devices 46, 47 are connected to a pressure It is connected to a compressed air source.

[0064] The inlet of the homogenizer 32 is fluidly connected to the first reservoir outlet 18 . The outlet of the homogenizer 32 is fluidly connected to a second reservoir 40 and a first delivery device. The outlet of the third reservoir 86 fluidly communicates with the second delivery device 47. is connected to

[0065] During use, the oocyst solution 82 is pumped from the first reservoir 12 by the pump 20. The homogenizer is controlled by a pressure valve 28. The high pressure homogenizer 32 includes a high pressure source 26 through which the oocysts in the solution 82 are introduced into the inlet 36. The homogenizer 32 moves the solution 82 through a small opening (not shown). (not shown) to disrupt at least some of the oocyst membranes, resulting in The solution is then passed through an outlet 38 to release at least some of the sporocysts. The alumina in a solution containing calcium chloride is transferred to a second container 40 through a port 42. The cysts, disrupted membranes, and sporocysts result in an altered solution 85. The resulting solution 85 is then transferred directly to the first nozzle 50 .

[0066] In another configuration, the high pressure homogenizer 32 can be directly connected to the delivery device 46. In this manner, the solution produced by the homogenizer 32 is The medicines will be delivered directly to the hospital, rather than being temporarily stored in a warehouse.

[0067] When animals, particularly one-day-old hatchlings, are sprayed, first and second nozzles 50, 51 is opened. In both the first and second nozzles 50, 51, compressed air is directed at the surface of the young bird. A spray profile is created for each of both solutions 85, 90 which mix and form a gel. When both solutions85,90 are mixed in the young birds, they produce oocysts and released sporozoites. They form a gel 87 that contains the cysts. This gel slows down the rate of dehydration and also aids in grooming. Preferably, the solutions 85, 90 are administered to young pups, thereby increasing the chances of ingestion by the animals. The drug is sprayed onto one or more mucosal areas, i.e., the eyes and / or beak.

[0068] As described above with respect to the second gel embodiment 110 or the third gel embodiment 120 Either a calcium chloride solution or a sodium alginate solution is then pumped through the delivery device. Solution 8 may be mixed with the oocyst-based vaccine before being pumped. 5, 90 to achieve the same result, i.e., spraying the gel onto the surface of the animal subject. They may be sprayed independently in any order or simultaneously to form the base mixture.

[0069] The third gel embodiment 120 uses a homogenizer 32 as the processing system 24. As described above, other processes may be used to obtain the modified solution 85 of the third gel embodiment 120. It is further understood that the above third gel is expected to be able to be used as a substitute for the above-mentioned gel. In the embodiment 120, the solution 85 and the solution 90 are respectively fed to the processing system 24 and the third reservoir. 4, including being transferred directly from the bar 86, and the solutions 85, 90, Either or both of the above may first be transferred to a temporary holding tank prior to delivery. It is understood that additional processing systems will be available. PCT Application No. PCT / US19 / 41178, James Hutchins See et al.

[0070] All of the embodiments described herein may be applied to animals individually or all at once. It should be noted that the embodiments described herein are the gel embodiments (1), (2) and (3). ) or (3), which receives the solution in a gel form. It is understood that this may apply to large populations of young birds or other animals contained in containers (such as will be done.

[0071] The systems and methods disclosed herein can be adapted for use in aquaculture. Gel beads containing nutrients, medicines, or vaccines can be created in situ, It is introduced into fish tanks or open water bodies containing farmed fish and consumed there. Examples of ia include, but are not limited to, E. aurati, E. baueri, E. le pidosirenis, E.leucisci, E.rutili, and E.vana si. Suitable for facilitating the release of more infectious life stages for vaccination purposes. If available, the shearing process can be applied to these species. Vaccines for E. coli are administered as gelatinocytes dispensed into aquaria or water for consumption by fish. The formulation may be administered using a gel forming process using a gel.

[0072] 5.6.Application of the two-component gel method Combination of two low viscosity components forms a protective gel coating in situ are useful in a variety of applications, such as frost protection for plants or wound dressings for humans or animals. Drones can capture entire plants or trees in orchards, as well as the flowers of individual plants. or on-the-fly to sick or injured animals in the herd. ) can be specifically and efficiently incorporated into the visual system with a two-component gel delivery system. The low viscosity of the individual liquid components allows for a high pressure system to be used to directly deliver the gel. In comparison, this facilitates low pressure delivery.

[0073] The gel system can be used as a frost protection system for plants and can be applied in a small spray bottle or The system could deliver the drug to individual animals in a herd. Vaccines and medicines could be used to deliver to livestock animals such as cattle or horses. This system could be used to deliver medicines to humans. Applications could include the treatment of wounds or burns. One advantage of two-component gel delivery for wound or burn treatment is the reduced risk of infection of sensitive tissue. For the treatment of burns, antibiotics or The two aqueous solutions containing local anesthetics are sprayed onto the burn without the need for direct contact with the burn. tu will form a gel.

[0074] The following examples further illustrate the disclosure and are not intended to limit the scope. This disclosure is not limited to the particular embodiments described, and as such may, of course, vary. It should be understood that the terminology used herein may be used to describe specific embodiments. For clarity purposes only, the scope of the present disclosure is limited only by the appended claims. It should also be understood that the present invention is not intended to be limiting, but is instead defined as such. EXAMPLES

[0075] 6. Working Example 6.1.Preliminary study of two-component gel While considering various nozzles for applying oocyst vaccine to one-day-old chicks, The researchers sought ways to visualize the spray patterns produced by the mosquito nets. A paper card (Syngenta) was used, but the pattern formed was not particularly As an alternative method, a petri dish containing 2% argon was used. A method was developed to fill the nebulizer with a 2 mL pool of sodium phosphate. , about 3% calcium chloride, red food coloring, and in some cases, oocyst vaccines. The spray was delivered from a nozzle into a pool of sodium alginate, and two Upon contact of the solutions, a red gel was formed. The resulting gel pattern was analyzed, particularly under a microscope. After visualizing the oocysts contained within the gel under a microscope, this two-component gel system was used to An option for delivering vaccines to birds has been developed. The gel creates a protective barrier around the oocysts. This may result in the formation of a cyst network, potentially allowing the oocysts to be used for grooming over a longer period of time. Both components of the formulation have low viscosity and are similar to those currently used for delivery of oocyst vaccines. Low viscosity aqueous solutions offer advantages over the highly viscous gel formulations currently used. This has advantages over current high viscosity gels, such as increased viscosity and ease of dispensing. In addition to providing a high level of protection, the gel formulation reduces splashback and improves the This is expected to help maintain the administered substance in the body.

[0076] Initial experiments in delivering vaccine to chicks via a two-component gel method used 3% calcium chloride and 2% sodium alginate was used. In some cases the gel appeared on the chicks' feathers after a few minutes. It was observed that the stability was lost at 0.05%. When the calcium chloride concentration was increased from 3% to 5%, It maintains its structure more uniformly and provides a more protective environment for the oocysts or sporocysts. The alginate was dispensed into Petri dishes and allowed to stand for 3-4 hours. Or a 5% solution of calcium chloride was added to the alginate drop. A gel immediately formed. However, when the plate was tilted upwards, the combination of 3% calcium chloride The gel flowed down the plate, whereas the 4 and 5% calcium chloride gels stayed in place. Currently, calcium chloride concentrations of approximately 3.5-3.8% are used.

[0010] Broiler chickens were given a 1x dose of coccidiosis vaccine as eye drops (positive control). The birds were administered either by eye spray or by ocular spray, which was performed using a stationary position between two nozzles. The nozzle used an atomizing air configuration. The spray was directed at the chicken's eyes. The treatments were: Released sporocysts and residual oocysts produced by manual shaking with glass beads For additional details, see P filed on July 10, 2019. CT Application No. PCT / US19 / 41178, James Hutchins et al. For one treatment, the first session was administered with 2% sodium alginate solution. and the second set administered the vaccine in a 3.5% calcium chloride solution. A nozzle was used. The vaccine administered by spray was 100uL in total (per eye). The vaccine administered via eye drops was delivered in a total of 50uL (per eye). After vaccination, birds were placed in cages and Birds were grown under standard conditions until day 7. The birds were euthanized and the intestines were removed from each bird on day 7. The contents were collected. The oocysts in the feces were identified by the McMaster flotation chamber method. The infection rates are shown below.

[0011] Table 1: Infection rates by species of chickens vaccinated by eye spray [Table 1]

[0012] The results showed that the infection rate of E. maxima and E. acervulina increased with gel treatment. The positive and negative control results were as expected.

[0077] 6.3. Gel Delivery of Vaccines Containing Sporocysts In a separate experiment, the difference between vaccination with sporocysts and oocysts can be seen. In this experiment, the release of sporocysts was achieved by suspension of multi-species oocysts together with 4 mm glass beads. This was achieved by shaking the suspension by hand. A solution of 2% sodium alginate and oocysts alone was administered to the facial mucosa on the day of hatch. The first set was administered in 3.0% calcium chloride solution, and the second set was administered in 3.0% calcium chloride solution. Two sets of nozzles were used, one for the first solution and the other for the second solution. Upon contact, a gel is formed. The formation of the gel allows the oocyst / sporocyst vaccine to Keeps birds hydrated for longer compared to regular water-based sprays, extending the potential grooming time for your bird The hypothesis is that this will improve the performance of the device. The results of this experiment are shown in the table below.

[0078] Table 2: Response of birds sprayed with oocysts in gel or sporocysts with residual oocysts. Frequency and Amplitude [Table 2]

[0079] No oocysts were observed in the intestinal contents of untreated control birds, whereas positive controls inoculated by eye drops Illumination resulted in higher frequency and amplitude of infectivity than the experimental spray treatment groups. These results The sporocysts in the gel formulation outperformed the oocysts alone in both frequency and amplitude of response. This indicates that:

[0080] 7. Generalized Statements of Disclosure The following numbered statements provide a general description of the disclosure and are incorporated in the accompanying claims: It is not intended to limit the scope of the present invention.

[0081] Statement 1: A system for delivering a gel to a surface, comprising: in a first solution a first container containing a binder / crosslinker in a second solution; a second container containing a gelling component in a second solution; and a delivery device in fluid communication with the first container and the second container, the delivery device outlet A delivery device having

[0082] Statement 2: The first solution is transferred from the first container to the delivery device outlet. a first spray is generated at a predetermined location, and the second solution is sprayed forward from the second container. the delivery device outlet is moved to generate a second spray at the predetermined location; the statement that the one solution and the second solution react to form a gel in said predetermined location. 1. The system described in 1.

[0083] Statement 3: The gelling component is sodium alginate and the binder / crosslinker The system of any of statements 1-2, wherein the bridging agent is calcium chloride.

[0084] Statement 4: The first solution or the second solution is either a solution or a suspension. The system of any one of statements 1 to 3, further comprising a target product as a target product.

[0085] Statement 5: The product of interest is intended for use in food, agriculture, manufacturing, chemical, biochemical, military, aerospace, Aerospace, pharmaceutical, cosmetics, nutritional supplements, printing, or a combination of these industries The system according to statement 4, which applies to at least one

[0086] Statement 6: The intended product is a food product, a herbicide, a pesticide, a pharmaceutical, a biological product , cosmetics, dietary supplements, pharmaceuticals, coatings, inks, paints, or combinations thereof The system according to statement 4.

[0087] Statement 7: The method according to statement 4, wherein the product of interest is a vaccine. system.

[0088] Statement 8: The method according to statement 7, wherein the vaccine comprises oocysts. Stem.

[0089] Statement 9: Any of statements 7 to 8, wherein the vaccine comprises sporocysts. 2. The system according to claim 1 .

[0090] Statement 10: The calcium chloride is present in a concentration of about 1% to about 5%. 3. The system according to claim 2,

[0091] Statement 11: The sodium alginate is present in a concentration of about 0.5% to about 5%. The system according to statement 3.

[0092] Statement 12: The method of any one of statements 1 to 11, wherein the delivery device is a nebulizer. The system according to any one of the preceding claims.

[0093] Statement 13: A method for delivering a gel to a surface, comprising the steps of: first providing a first container containing a binder / crosslinker in a solution of; and a gelling component in a second solution. a transfer device in fluid communication with said first container and said second container; providing a delivery device; discharging said first solution from said first container into said delivery device; moving the mixture through the opening onto a surface at a predetermined position; and forming a gel. The second solution is transferred from the second container through the outlet of the delivery device onto a surface at a predetermined location. To move.

[0094] Statement 14: The first solution or the second solution is either a solution or a suspension. The method according to claim 13, further comprising the desired product.

[0095] Statement 15: The product of interest is for use in food, agriculture, manufacturing, chemical, biochemical, military, Aerospace, pharmaceuticals, cosmetics, nutraceuticals, printing, or a combination of these industries 15. The method according to claim 14, wherein the method is applied to at least one of the following:

[0096] Statement 16: The intended product is a food product, a herbicide, a pesticide, a medicine, a biological product, cosmetics, dietary supplements, medicines, coatings, inks, paints, dyes, or any of the above 15. The method according to statement 14, which is a combination.

[0097] Statement 17: The method according to statement 14, wherein the product of interest is a vaccine. Method of posting.

[0098] Statement 18: The vaccine according to statement 17, comprising oocysts. How to.

[0099] Statement 19: The vaccine comprises sporocysts, Statements 17-1 8. A method according to any one of claims 7 to 8.

[0100] Statement 20: A gel solution formed in situ, the gel comprising A first solution containing a binder / crosslinker is applied to the surface at a predetermined location, and and a second solution comprising a gelling component is applied to form a gel solution.

[0101] It should be understood that the above description is merely representative of example embodiments and examples. For the convenience of the reader, the above description is presented as a limited number of representative examples of all possible embodiments. That is, the focus is on examples that teach the principles of the disclosure. This description does not cover all possible variations. It is not intended to exhaustively list all of the above-described combinations of the above-described variations. It is not intended that alternative embodiments be presented in any particular portion of this disclosure. There may be other possible or further undescribed alternative embodiments in some parts. The availability of such alternative embodiments should not be construed as a disclaimer of those alternative embodiments. Those skilled in the art will recognize that many of these undescribed embodiments are not merely an example of application of the principles of the present disclosure. It will be understood that the present disclosure includes differences in technique and materials, not just differences. is intended to be limited to no less than the scope of the following claims and equivalents. It's not something like that.

[0102] Incorporation by Reference

[0103] All references, articles, publications, patents, patent publications, and patent applications cited herein are the property of their respective owners. The applications are incorporated by reference in their entirety for all purposes. For references, articles, publications, patents, patent publications, and patent applications cited in The reference constitutes valid prior art or is part of the general knowledge in any country in the world This disclosure is not to be construed as an admission or suggestion that the invention constitutes any While described in detail herein, the foregoing description is intended to be illustrative and not limiting in scope. It should be understood that the present invention is not intended to limit the scope of the present invention. Other aspects, advantages, and modifications are within the scope of the appended claims. All publications, patents, and other references cited herein are within the scope of the appended claims. Each publication or patent application is specifically and specifically indicated to be incorporated by reference. No. 6,393,945, which are incorporated herein by reference as if otherwise indicated.

Claims

1. A system for delivering a gel to a surface, comprising: a first container containing a binder / crosslinker in a first solution; a second container containing a gelling component in a second solution; and a delivery device in fluid communication with the first container and the second container, the delivery device outlet A delivery device having

2. The first solution is transferred from the first container to the delivery device outlet, and a predetermined a first spray at a location where the second solution is sprayed from the second container through the delivery device outlet; and generating a second spray at the predetermined location, the first solution and the second solution are mixed. The system of claim 1 , wherein the liquid reacts to form a gel at the predetermined location.

3. The gelling component is sodium alginate and the binder / crosslinker is calcium chloride. The system of claim 1 ,

4. The first solution or the second solution is dissolved in water to obtain a desired product as either a solution or a suspension. The system of claim 1 further comprising:

5. The product of interest may be food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, cosmetic, Applicable to at least one of the following industries: food products, nutritional supplements, printing, or a combination thereof The system according to claim 4 .

6. The product of interest may be a food product, a herbicide, a pesticide, a pharmaceutical, a biological product, a cosmetic, a nutritional supplement, 4. The composition according to claim 4, which is a food product, a drug product, a coating agent, an ink, a paint, or a combination thereof. The system described in

7. The system of claim 4 , wherein the product of interest is a vaccine.

8. The system of claim 7 , wherein the vaccine comprises oocysts.

9. The system of claim 7 , wherein the vaccine comprises sporocysts.

10. 4. The system of claim 3, wherein the calcium chloride is present at a concentration of about 1% to about 5%. 。

11. 4. The method of claim 3, wherein the sodium alginate is present at a concentration of about 0.5% to about 5%. system.

12. The system of claim 1 , wherein the delivery device is a sprayer.

13. A method of delivering a gel to a surface, comprising the steps of: providing a first container containing a binder / crosslinker in a first solution; providing a second container containing a gelling component in a second solution; providing a delivery device in fluid communication with the first container and the second container; The first solution is delivered from the first container through an outlet of the delivery device to a surface at a predetermined location. moving it onto a surface; and The second solution is then passed from the second container through an outlet of the delivery device to form a gel. and move it through the device and into position on the surface.

14. The first solution or the second solution is dissolved in water to obtain a desired product as either a solution or a suspension. The method of claim 13 further comprising:

15. The product of interest may be food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, cosmetic, Applicable to at least one of the following industries: food products, nutritional supplements, printing, or a combination thereof The method according to claim 14, wherein

16. The product of interest may be a food product, a herbicide, a pesticide, a pharmaceutical, a biological product, a cosmetic, a nutritional supplement, Claims that are food, medicine, coating, ink, paint, dye, or combinations thereof Item 15. The method according to item 14.

17. 15. The method of claim 14, wherein the product of interest is a vaccine.

18. 20. The method of claim 17, wherein the vaccine comprises oocysts.

19. The method of claim 17 , wherein the vaccine comprises sporocysts.

20. A gel solution formed in situ, the gel being applied to a surface at a predetermined location. A first solution containing a binder / crosslinker and a gelling agent are applied to the surface at a predetermined location. and a second solution containing the component (s).

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